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Rabies is a lethal zoonotic disease caused by a single-stranded, negative-sense RNA virus of the Lyssavirus genus, within the family Rhabdoviridae. Its primary mode of transmission to humans is through bites or saliva-contaminated scratches from infected mammals such as dogs, bats, raccoons, or foxes. Transmission can also occur if infectious saliva contacts abraded skin or intact mucous membranes, including the conjunctiva.Viral Entry and Early ReplicationOnce introduced at the bite or scratch...
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    Area of Science:

    • Virology
    • Structural Biology
    • Neuroscience

    Background:

    • Alphaviruses are significant human pathogens transmitted by arthropods.
    • Eastern equine encephalitis virus (EEEV) is a highly virulent alphavirus causing severe neurological sequelae.
    • EEEV and Semliki forest virus (SFV) utilize brain-expressed very-low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as cellular entry receptors.

    Conclusions:

    • Different alphaviruses employ distinct molecular strategies to interact with the same cellular receptor.
    • The flexible binding modes and small interaction footprints with LDLR-related proteins facilitate their adoption as receptors by diverse viruses.
    • This adaptability suggests a low evolutionary barrier for viruses acquiring LDLR-family proteins as cellular receptors.